Prognostic Value of Routinely Measured Inflammatory Biomarkers in Older Cancer Patients: Pooled Analysis of Three Cohorts

BACKGROUND: The prognostic assessment of older cancer patients is complicated by their heterogeneity. We aimed to assess the prognostic value of routine inflammatory biomarkers. METHODS: A pooled analysis of prospective multicenter cohorts of cancer patients aged >/=70 was performed. We measured CRP and albumin, and calculated Glasgow Prognostic Score (GPS) and CRP/albumin ratio. The GPS has three levels (0 = CRP /= 35 g/L, i.e., normal values; 1 = one abnormal value; 2 = two abnormal values). One-year mortality was assessed using Cox models. Discriminative power was assessed using Harrell's C index (C) and net reclassification improvement (NRI). RESULTS: Overall, 1800 patients were analyzed (mean age: 79 +/- 6; males: 62%; metastases: 38%). The GPS and CRP/albumin ratio were independently associated with mortality in patients not at risk of frailty (hazard ratio [95% confidence interval] = 4.48 [2.03-9.89] for GPS1, 11.64 [4.54-29.81] for GPS2, and 7.15 [3.22-15.90] for CRP/albumin ratio > 0.215) and in patients at risk of frailty (2.45 [1.79-3.34] for GPS1, 3.97 [2.93-5.37] for GPS2, and 2.81 [2.17-3.65] for CRP/albumin ratio > 0.215). The discriminative power of the baseline clinical model (C = 0.82 [0.80-0.83]) was increased by adding GPS (C = 0.84 [0.82-0.85]; NRI events (NRI+) = 10% [2-16]) and CRP/albumin ratio (C = 0.83 [0.82-0.85]; NRI+ = 14% [2-17]). CONCLUSIONS: Routine inflammatory biomarkers add prognostic value to clinical factors in older cancer patients

Mise au point d'un modèle d'anévrisme fusiforme carotidien chez le lapin. Etude du remodelage artériel (élastine, MMPs, cytokines) après thérapie cellulaire par fibrosblastes gingivaux

L'anévrisme abdominal aortique (AAA) se caractérise par une protéolyse des macromolécules de la média (élastine, collagène), une inflammation transmurale et une apoptose des cellules musculaires lisses. Nous avons voulu développer un modèle d'anévrisme fusiforme chez le lapin afin de tester la faisabilité et l'effet d'une thérapie cellulaire endovasculaire percutanée par des fibroblastes gingivaux (FG). Ce modèle a été induit par incubation d'élastase dans la lumière de l'artère carotide, et la thérapie a été réalisée 28 jours plus tard par injection de fibroblastes gingivaux dans la paroi anévrismale. L'évaluation de l'efficacité thérapeutique (étude morphomètrique, densité d'élastine, analyse biomoléculaire des metalloprotéases, de leur inhibiteur tissulaires et des cytokines) a montré la diminution de la taille de l'anévrisme, la préservation du réseau élastique, l'inhibition des MMP-1 et -9, due à l'augmentation du TIMP-1 et l'inhibition des cytokines inflammatoires. Les FG sont donc des candidats pour la thérapie de l'AAAAbdominal aortic aneurysm (AAA) is characterized by an increased proteolysis of the essential macromolecules of the media (elastin, collagen), transmural inflammation and apoptosis of smooth muscular cells. We aimed to develop an fusiform aneurysm model in rabbit in order to evaluate the feasibility and the efficiency of percutaneous endovascular cell therapy with gingival fibroblasts (GF). We induced this model by incubation of elastase in the lumen of rabbit carotid arteries. Endovascular cell therapy was performed 28 days later by transplantation of GF in the arterial aneurysmal wall. Analysis of the results (arterial morphometry, elastin density, biomolecular study of metalloprotei-nases, their tissue inhibitor and cytokines) shows the decrease of the aneurysmal size, the preservation of the elastic network, the inhibition of MMP-1 and -9, consequently to TIMP-1 increase and the inhibition of inflammatory cytokines. Therefore GF are potential candidates for the endovascular therapy of AAA.PARIS5-BU Méd.Cochin (751142101) / SudocSudocFranceF

LE TABAGISME (INCIDENCES SUR L'ETAT DE SANTE GENERAL ET B UCCO-DENTAIRE)

MONTROUGE-BUFR Odontol.PARIS5 (920492101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Depressive Symptom Profiles and Survival in Older Patients with Cancer: Latent Class Analysis of the ELCAPA Cohort Study

International audienceBackground: The expression of depressive symptoms in older people with cancer is heterogeneous because of specific features of age or cancer comorbidity. We aimed to identify depressive symptom profiles in this population and describe the associated features including survival.Materials and methods: Patients ≥70 years who were referred to geriatric oncology clinics were prospectively included in the ELCAPA study. In this subanalysis, depressive symptoms were used as indicators in a latent class analysis. Multinomial multivariable logistic regression and Cox models examined the association of each class with baseline characteristics and mortality.Results: For the 847 complete-case patients included (median age, 79 years; interquartile range, 76-84; women, 47.9%), we identified five depressive symptom classes: "no depression/somatic only" (38.8%), "no depression/pauci-symptomatic" (26.4%), "severe depression" (20%), "mild depression" (11.8%), and "demoralization" (3%). Compared with the no depression/pauci-symptomatic class, the no depression/somatic only and severe depression classes were characterized by more frequent comorbidities with poorer functional status and higher levels of inflammation. "Severe" and "mild" depression classes also featured poorer nutritional status, more medications, and more frequent falls. Severe depression was associated with poor social support, inpatient status, and increased risk of mortality at 1 year (adjusted hazard ratio, 1.62, 95% confidence interval, 1.06-2.48) and 3 years (adjusted hazard ratio, 1.49; 95% confidence interval, 1.06-2.10).Conclusion: A data-driven approach based on depressive symptoms identified five different depressive symptom profiles, including demoralization, in older patients with cancer. Severe depression was independently and substantially associated with poor survival.Implications for practice: Older patients with cancer present with distinct profiles of depressive symptomatology, including different severity levels of depression and the demoralization syndrome. Clinicians should use a systematic assessment of depressive symptoms to adequately highlight these distinct profiles. Geriatric and oncological features are differently associated with these profiles. For instance, severe depression was associated with more frequent comorbidities with poorer functional, poor nutritional status, polypharmacy, frequent falls, inpatient status and poor social support. Also, severe depression was independently and substantially associated with poor survival so that the identification and management of depression should be considered a high priority in this population